TAZORAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAZORAC (TAZORAC).
Tazarotene is a retinoid prodrug that is converted to its active metabolite, tazarotenic acid, which binds to retinoic acid receptors (RAR-β, RAR-γ) with high affinity, modulating gene expression involved in cell proliferation, differentiation, and inflammation.
| Metabolism | Tazarotene is rapidly metabolized via ester hydrolysis to its active metabolite, tazarotenic acid. Further metabolism includes oxidation and conjugation. The metabolic pathways involve esterases and cytochrome P450 (CYP) enzymes, primarily CYP2C8, with minor contributions from CYP3A4 and CYP2C9. |
| Excretion | Primarily fecal: approximately 60-70% eliminated in feces (as metabolites), renal excretion accounts for <10% as unchanged drug and metabolites, with <1% as unchanged tazarotenic acid. |
| Half-life | Terminal elimination half-life of tazarotenic acid is approximately 18 hours (range 7-30 hours) after topical application, allowing once-daily dosing; systemic exposure is low due to extensive protein binding and slow clearance. |
| Protein binding | Highly protein-bound (>99%), primarily to albumin and also to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution for tazarotenic acid is approximately 1.5 L/kg (range 0.5-3.0 L/kg), indicating distribution into total body water and extensive tissue binding, particularly in skin. |
| Bioavailability | Bioavailability after topical application: 1-5% of the applied dose is absorbed systemically (based on urinary and fecal recovery of radiolabeled drug), with minimal systemic exposure; oral bioavailability has been studied but is not clinically relevant as the drug is used topically. |
| Onset of Action | Onset of clinical effect is within 1 to 2 weeks after topical application for plaque psoriasis; for acne vulgaris, improvement may be seen within 4 weeks. |
| Duration of Action | Duration of action lasts for the dosing interval (24 hours), with sustained improvement over weeks to months of continued therapy; residual effects may persist for several days after discontinuation due to drug retention in skin. |
Apply a pea-sized amount to affected areas once daily in the evening. Tazorac is available as a 0.05% or 0.1% gel or cream. For plaque psoriasis, the 0.1% gel is typically used. For acne, the 0.1% cream or gel is started, then decreased to 0.05% if irritation occurs.
| Dosage form | CREAM |
| Renal impairment | No specific dose adjustment recommended for renal impairment. Use with caution in severe renal disease due to lack of data. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment. Use with caution in severe hepatic disease due to lack of data. |
| Pediatric use | Not recommended for use in children <12 years of age for acne; safety and efficacy not established. For psoriasis, use in adolescents ≥12 years: apply 0.05% or 0.1% gel once daily; initiate with lower concentration if irritation is a concern. |
| Geriatric use | No specific dose adjustment; use age-appropriate formulation. Elderly may have increased risk of skin irritation; consider using lower concentration (0.05%) and monitor skin tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAZORAC (TAZORAC).
| Breastfeeding | Contraindicated due to potential for serious adverse effects in nursing infants. M/P ratio not determined; tazarotene and its metabolites are excreted in human milk. |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of major fetal malformations including CNS, cardiovascular, and craniofacial defects. Second/third trimester: Continued teratogenicity; associated with increased risk of spontaneous abortion and preterm birth. |
| Fetal Monitoring |
■ FDA Black Box Warning
Tazarotene is contraindicated in women who are or may become pregnant. Women of childbearing potential must have a negative pregnancy test within 2 weeks prior to starting therapy and use effective contraception. If pregnancy occurs, treatment should be discontinued immediately.
| Serious Effects |
Absolute: Pregnancy or women planning pregnancy. Hypersensitivity to tazarotene or any component of the formulation. Relative: Nursing mothers; severe eczema; open wounds or sunburned skin.
| Precautions | Avoid excessive exposure to UV light (sunlight, tanning lamps). Use with caution in patients with eczema or sunburned skin. Photosensitivity reactions may occur. Avoid contact with eyes, mouth, and mucous membranes. May cause skin irritation (e.g., redness, peeling, burning). Not recommended for use on intertriginous areas or with occlusive dressings. |
Loading safety data…
| Pregnancy test before initiation, monthly during therapy, and 1 month after discontinuation. Use effective contraception during treatment and for 1 month after last dose. |
| Fertility Effects | No definitive human data; animal studies show no impairment of fertility at clinically relevant doses. |